Schizophrenia (SZ) is a common, lifelong, disabling disorder. Its treatment remains unsatisfactory across the world. Thus, research into its causation and pathogenesis is needed urgently. Based on the substantial heritability (~70%), gene mapping efforts are in progress. Credible risk variants have been found, but the identified factors explain only a small proportion of the estimated heritability. Even the limited information has highlighted novel pathways for SZ genesis, so additional gene mapping studies are warranted. Such efforts will require many thousands of participants in outbred populations. Our plan with an inbred population promises novel insights with more modest effort. We will build on a collaborative R21 project between investigators at the University of Pittsburgh (PITT) and Mansoura University (MU, Egypt). In the Nile delta region, we have found increased consanguinity among patients with SZ compared with unaffected controls. The results are consistent with recessive genetic risk factors for SZ. We will employ a powerful tool called homozygosity by descent (HBD) analysis that has been successfully used to map several hundred recessive Mendelian diseases and genetically more complex disorders like autism and intellectual disability. Our preliminary studies suggest similar success for SZ. Our proposal is novel also because most SZ gene mapping studies have been conducted among Caucasian ancestry participants. Investigations of other ethnic groups, particularly those with unusual patterns of inheritance may yield useful, complementary insights. Through the NIMH genetics repository, we will share samples and data with members of the scientific community, further increasing the impact of our work. There is increasing interest in harnessing genomics research, as well as recognition of the

Public Health Relevance

of consanguinity in the Middle East. Accordingly, we have trained and assisted our Egyptian colleagues to establish a genetics research group at MU, including a molecular genetics laboratory. We have published our work and obtained other funds to start additional research. Thus, we have successfully used our research as a vehicle for research infrastructure and capacity building at MU. Our goal is to scale up the genetics research at MU by implementing state of the art genetic analyses, including computing and bioinformatics. The resources and expertise garnered through this work will facilitate research into other diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
4R01MH093246-05
Application #
9127361
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Addington, Anjene M
Project Start
2012-09-20
Project End
2017-07-31
Budget Start
2016-08-01
Budget End
2017-07-31
Support Year
5
Fiscal Year
2016
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Psychiatry
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Bhatia, Triptish; Wood, Joel; Iyengar, Satish et al. (2018) Emotion discrimination in humans: Its association with HSV-1 infection and its improvement with antiviral treatment. Schizophr Res 193:161-167
D'Aiuto, Leonardo; Williamson, Kelly; Dimitrion, Peter et al. (2017) Comparison of three cell-based drug screening platforms for HSV-1 infection. Antiviral Res 142:136-140
Nimgaonkar, V L; Prasad, K M; Chowdari, K V et al. (2017) The complement system: a gateway to gene-environment interactions in schizophrenia pathogenesis. Mol Psychiatry 22:1554-1561
John, Jibin; Kukshal, Prachi; Bhatia, Triptish et al. (2017) Possible role of rare variants in Trace amine associated receptor 1 in schizophrenia. Schizophr Res 189:190-195
Mansour, Hader A; Wood, Joel; Chowdari, Kodavali V et al. (2017) Associations between period 3 gene polymorphisms and sleep- /chronotype-related variables in patients with late-life insomnia. Chronobiol Int 34:624-631
Watson, Annie; Pribadi, Mochtar; Chowdari, Kodavali et al. (2016) C9orf72 repeat expansions that cause frontotemporal dementia are detectable among patients with psychosis. Psychiatry Res 235:200-2
John, Jibin; Bhatia, Triptish; Kukshal, Prachi et al. (2016) Association study of MiRSNPs with schizophrenia, tardive dyskinesia and cognition. Schizophr Res 174:29-34
Ibrahim, Ibtihal; Salah, Hala; El Sayed, Hanan et al. (2016) Hepatitis C virus antibody titers associated with cognitive dysfunction in an asymptomatic community-based sample. J Clin Exp Neuropsychol 38:861-8
Sewilam, Ahmed M; Watson, Annie M M; Kassem, Ahmed M et al. (2015) Suggested avenues to reduce the stigma of mental illness in the Middle East. Int J Soc Psychiatry 61:111-20
Das, D K; Tapias, V; D'Aiuto, L et al. (2015) Genetic and morphological features of human iPSC-derived neurons with chromosome 15q11.2 (BP1-BP2) deletions. Mol Neuropsychiatry 1:116-123

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